THE PRIMARY STRUCTURE OF HUMAN UROGASTRONE

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Abstract
Urogastrone is a potent inhibitor of gastric acid secretion present in human urine. Its existence has been known for over 30 yr but it has only recently been isolated in a sufficiently pure form for detailed structural studies to be undertaken. Two separate polypeptides .beta.- and .gamma.-urogastrone were isolated. The structures were established by carrying out enzymic degradations of S-carboxymethyl and S-carboxamidomethyl derivatives with trypsin, chymotrypsin, thermolysin and a protease derived from the fungus Armillaria mellea. Sequences of the smaller peptides obtained were determined by the dansyl Edman method. Partial acid hydrolysis of urogastrone itself gave fragments containing single intact disulfide bonds, and oxidation then allowed the direction of individual bonds to be established. .beta.-Urogastrone was a 53-amino acid residue polypeptide containing 3 disulfide bonds, and .gamma.-urogastrone had an identical sequence but lacked the C-terminal arginine residue. Urogastrone is structurally related to mouse epidermal growth factor [EGF] in that 37 of the 53 residues were commonly located in each polypeptide. As both peptides had similar effects on gastric acid secretion and on epidermal growth, urogastrone was a human epidermal growth factor. The 16 variable residues were spread across the molecule, all apart from 2 were compatible with single base changes in the triplet codons, and the overall effect was to make urogastrone more acidic than EGF. The smallest biologically active unit has not been defined, but at least 6 residues can be removed from the C-terminus without causing a reduction in potency.